IMFINZI - LYNPARZA (durvalumab/olaparib) - Endometrial cancer
Opinions on drugs -
Posted on
Feb 19 2025
Reason for request
Indication extension
Summary of opinion
Favourable opinion for reimbursement in the indications:
IMFINZI (durvalumab): “IMFINZI in combination with carboplatin and paclitaxel is indicated for the first-line treatment of adults with primary advanced or recurrent endometrial cancer who are candidates for systemic therapy, followed by maintenance treatment with IMFINZI in combination with olaparib in endometrial cancer that is mismatch repair proficient (pMMR).”
LYNPARZA (olaparib): “LYNPARZA in combination with durvalumab is indicated for the maintenance treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair proficient (pMMR) whose disease has not progressed on first-line treatment with durvalumab in combination with carboplatin and paclitaxel.”
Clinical Benefit
Substantial
The Committee deems that the clinical benefit of IMFINZI (durvalumab) concentrate for solution for infusion and LYNPARZA (olaparib) film-coated tablets is substantial in the MA indications.
Clinical Added Value
minor
Considering:
evidence of a superiority in the phase 3 DUO-E study of durvalumab in combination with paclitaxel + carboplatin chemotherapy in the induction phase, followed by maintenance therapy with durvalumab in combination with olaparib in terms of radiological progression-free survival in the ITT population with an HR = 0.55 (CI95% = [0.43; 0.69]; p < 0.0001). The median progression-free survival was 15.1 months (CI95% = [12.6; 20.17]) in the durvalumab + olaparib group versus6 months, (CI95% = [9.0; 9.9]) in the control group, i.e. an absolute difference of 5.5 months;
and despite:
the lack of evidence of a superiority of durvalumab in combination with paclitaxel + carboplatin chemotherapy in the induction phase, followed by maintenance therapy with durvalumab in combination with olaparib, in terms of overall survival, in the ITT population (including 80% pMMR/MSS patients) assessed via an interim analysis;
the absence of an overall survival analysis specifically scheduled in the protocol for the pMMR/MSS patient subgroup in the DUO-E study;
the absence of robust comparative data, to date, supporting the therapeutic contribution of olaparib during the maintenance phase and in combination with durvalumab following an induction phase with carboplatin + paclitaxel chemotherapy in combination with durvalumab;
the data submitted, derived from an indirect comparison between the RUBY study (pivotal study for JEMPERLI (dostarlimab)) and the DUO-E study (pivotal study for the IMFINZI (durvalumab) and LYNPARZA (olaparib) combination) not enabling this treatment sequence to be better positioned compared to dostarlimab (JEMPERLI) in combination with chemotherapy followed by dostarlimab as monotherapy, due to methodological weaknesses making interpretation of the results difficult;
a safety profile particularly marked by grade 3 or 4 AEs, including haematological and gastrointestinal disorders, and the occurrence of syncope reported in 2/3 of patients in group C (durvalumab + olaparib);
the absence of any formal conclusion that can be drawn on quality of life (exploratory endpoint);
the Committee deems that IMFINZI (durvalumab) concentrate for solution for infusion and LYNPARZA (olaparib) film-coated tablets provide a minor clinical added value (CAV IV) compared to the carboplatin + paclitaxel combination in the treatment of adult patients with pMMR/MSS primary advanced or recurrent endometrial cancer (EC).
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